Jeddah Gut Club monthly meeting Yousef A. Qari Consultant Gastroenterologist King A.aziz University...

Jeddah Gut Club monthly meeting

Yousef A. QariYousef A. Qari

Consultant GastroenterologistConsultant Gastroenterologist

King A.aziz University HospitalKing A.aziz University Hospital

21/11/2005

Acute PancreatitisAcute Pancreatitis

100,000 hospitalizations annually in 100,000 hospitalizations annually in the United Statesthe United States

2000 (2%) directly related deaths from 2000 (2%) directly related deaths from

complicationscomplications 10% to 15% of deaths occur almost 10% to 15% of deaths occur almost

exclusively as a result of acute exclusively as a result of acute necrotizing pancreatitisnecrotizing pancreatitis

Mortality of acute pancreatitisof acute pancreatitis

The overall mortality remains The overall mortality remains approximately 5% to 10%approximately 5% to 10%

Rises to >40% if sterile necrosis Rises to >40% if sterile necrosis becomes superinfectedbecomes superinfected

Etiology of Acute pancreatitisEtiology of Acute pancreatitis

Gallstones 80% of cases. Alcohol

Endoscopic retrograde cholangiopancreatography (ERCP) Endoscopic retrograde cholangiopancreatography (ERCP) (overall 5% -20%)(overall 5% -20%)

Medications Trauma Neoplasms 10% of patients. Anatomic variants Metabolic problems

– HypercalcemiaHypercalcemia– HypertriglyceridemtaHypertriglyceridemta

Etiology of Acute pancreatitisEtiology of Acute pancreatitis

Rare causes of acute pancreatitisRare causes of acute pancreatitis

– Annular pancreasAnnular pancreas

– Autoimmune PancreatitisAutoimmune Pancreatitis

– Hereditary PancreatitisHereditary Pancreatitis

– Familial adenomatous polyposisFamilial adenomatous polyposis

– Pseudopapillary tumor of the pancreasPseudopapillary tumor of the pancreas

Classification of Acute pancreatitisClassification of Acute pancreatitis

Mild

( interstitial pancreatitis)

Majority of cases

Minimal organ failure Uneventful recovery

Responds well to supportive therapy

Severe

(necrotizing pancreatitis) Approximately 20% of patients Associated with

– Organ failure– local complications

Necrosis Infection Pseudocyst formation

Requires intensive monitoring and specific therapies and has a more guarded prognosis.

Clinical and radiologic scoring systems Since 1974Since 1974

19851985

1994 1994

New melliniumNew mellinium

Ranson's criteria [1] Ranson's criteria [1]

(APACHE II) system [2](APACHE II) system [2]

CT severity index [3,4]CT severity index [3,4]

Modified CT indexModified CT index– Multidetector-row Multidetector-row

computed tomography computed tomography (MDCT)(MDCT)

MRI severity indexMRI severity index– MRI with gadolinium MRI with gadolinium

(MRCPs) (MRCPs) Contrast enhanced EUSContrast enhanced EUS

1. Ranson JHC et al. Surg Gynecol Obstet 1974; 139:69-81 2. Knaus WA et al. Crit Care Med 1985; 13:818-829 3. Balthazar EJ et al Radiology1990; 174:331-336 4. Balthazar EJ et al , Radiology 1994; 193:297-306

The role of imaging in acute The role of imaging in acute pancreatitispancreatitis

Confirm the diagnosisConfirm the diagnosis

Identify necrosisIdentify necrosis

Determine the presence of complicationsDetermine the presence of complications– Fluid collections Fluid collections – Vascular abnormalitiesVascular abnormalities

Assessment of severityAssessment of severity

Multidetector-row computed Multidetector-row computed tomography (MDCT)tomography (MDCT)

The imaging study of The imaging study of choice for Acute choice for Acute pancreatitispancreatitis

Faster image acquisitionFaster image acquisition

Improved resolutionImproved resolution

Can be converted into Can be converted into three-dimensional three-dimensional reconstructionsreconstructions

CT severity index, by Balthazar in CT severity index, by Balthazar in

19941994 Focuses on the presence and degree of: Focuses on the presence and degree of:

– Pancreatic inflammation (fluid collections) Pancreatic inflammation (fluid collections) – Necrosis. Necrosis.

Successfully used to predict overall morbidity and Successfully used to predict overall morbidity and mortalitymortality

LimitationsLimitations

– Does not correlate significantly with Does not correlate significantly with Development of organ failureDevelopment of organ failure Extrapancreatic parenchymal complicationsExtrapancreatic parenchymal complications Peripancreatic vascular complicationsPeripancreatic vascular complications

– The interobserver agreement is approximating 75%. The interobserver agreement is approximating 75%.

CT severity index, by Balthazar in CT severity index, by Balthazar in 19941994

I - Pancreatic inflammationI - Pancreatic inflammation

Prognostic Indicator Prognostic Indicator PointPoint

ss

Normal pancreas Normal pancreas 00

Focal or diffuse enlargement of the pancreas Focal or diffuse enlargement of the pancreas 11

Intrinsic pancreatic abnormalities with inflammatory Intrinsic pancreatic abnormalities with inflammatory changes in peripancreatic fat changes in peripancreatic fat

22

Single, ill-defined fluid collection or phlegmon Single, ill-defined fluid collection or phlegmon 33

Two or more poorly defined collections or presence of Two or more poorly defined collections or presence of gas in or adjacent to the pancreas gas in or adjacent to the pancreas

44

CT severity index, by Balthazar in 1994CT severity index, by Balthazar in 1994

II - Pancreatic NecrosisII - Pancreatic Necrosis

Prognostic IndicatorPrognostic Indicator PointsPoints

None None 00

</= 30% </= 30% 22

> 30-50% > 30-50% 44

> 50% > 50% 66

Mild (score, 0-3 points), moderate (4-6 points), or severe (7-10 points).

Modified CT Severity IndexModified CT Severity Index by by Koenraad in 2004

I- Pancreatic inflammation I- Pancreatic inflammation


Normal pancreas Normal pancreas 00

Intrinsic pancreatic abnormalities with or without Intrinsic pancreatic abnormalities with or without inflammatory changes in peripancreatic fat inflammatory changes in peripancreatic fat 22

Pancreatic or peripancreatic fluid collection or Pancreatic or peripancreatic fluid collection or peripancreatic fat necrosis peripancreatic fat necrosis 44

Koenraad J et al, Am J Roentgenol 183(5):1261-1265, 2004

Modified CT Severity IndexModified CT Severity Index by by Koenraad in 2004

II- Pancreatic necrosisII- Pancreatic necrosis


None None 00

</= 30% </= 30% 22

> 30% > 30% 44

Extrapancreatic complications (one or more of Extrapancreatic complications (one or more of pleural effusion, ascites, vascular complications, pleural effusion, ascites, vascular complications, parenchymal complications, or gastrointestinal tract parenchymal complications, or gastrointestinal tract involvement) involvement)

22

Mild (0-2 points), moderate (4-6 points), or severe (8-10 points).

Correlation of Scoring Indexes With Correlation of Scoring Indexes With Patient OutcomePatient Outcome

VariablesVariablesStatistically significant Statistically significant

correlationcorrelationCT severity index CT severity index

(Balthazer)1994(Balthazer)1994Modified index Modified index

(Koenraad)2004(Koenraad)2004

The length of the hospital The length of the hospital Only with mild Only with mild severity groupsseverity groups

With all severity With all severity groupsgroups

The need for surgical or The need for surgical or percutaneous percutaneous interventions interventions

YesYes YesYes

The presence of infection The presence of infection YesYes YesYes

Development of organ Development of organ

failurefailure NoNo YesYes


Comparison between currently Comparison between currently accepted and modified CT severity accepted and modified CT severity indexesindexes

74-year-old man with acute pancreatitis. Axial contrast-enhanced CT scan shows:– One fluid collection in

anterior pararenal space– Minimal necrosis (< 30%).

On currently accepted CT severity index score was 5 (moderate pancreatitis)

On modified CT severity index score was 8 (severe pancreatitis)

MRCP-severity indexMRCP-severity index

Based on the existing Balthazar CTSI

Advantage:– Non-nephrotoxic contrast

agent gadolinium

– Ability to generate Ability to generate cholangiopancreatography cholangiopancreatography imageimage

– Detection of pancreatic Detection of pancreatic duct disruption with the duct disruption with the use of use of secretinsecretin

Arvanitakis M, et al.. Gastroenterology 2004; 126:715—723.

MRCP-severity indexMRCP-severity index

Correlated with

Serum level of C-reactive protein at 48 hours

Duration of hospitalization

Ranson score

Morbidity from local and systemic complications.

Arvanitakis M, et al.. Gastroenterology 2004; 126:715—723.

Acute Pancreatitis -- Prediction of Acute Pancreatitis -- Prediction of Severity using serum proteomic patternsSeverity using serum proteomic patterns

Patterns of low-molecular-mass biomarkersPatterns of low-molecular-mass biomarkers

Reveal an underlying, organ-specific pathology.Reveal an underlying, organ-specific pathology.

Sensitive and specific way to determine which Sensitive and specific way to determine which patients are likely to develop multisystem patients are likely to develop multisystem

failurefailure

Papachristou GI et al. Gastroenterology. 2004;126(suppl 2):A-29.

Acute Pancreatitis -- Prediction of Acute Pancreatitis -- Prediction of Severity using Severity using early hematocrit early hematocrit valuesvalues

Retrospective evaluation of 230 patientsRetrospective evaluation of 230 patients They found thatThey found that Absence of hemoconcentration at admission (defined Absence of hemoconcentration at admission (defined

as a hematocrit value of 43 or less) as a hematocrit value of 43 or less) Drop in 24-hour hematocrit level had a negative Drop in 24-hour hematocrit level had a negative

predictive value of 94.7% for the subsequent predictive value of 94.7% for the subsequent development of necrosis. development of necrosis.

Gardner TB et al. Am J Gastroenterol. 2004;99:S48.

Characterization of ICU patients using a model Characterization of ICU patients using a model based on the presence or absence of organ based on the presence or absence of organ dysfunctions and/or infectiondysfunctions and/or infection

Evidence of organ failureEvidence of organ failure

Respiratory failure – PaO2 of less than 60 mm Hg – Ventilatory support.

Cardiovascular system failure

– Systolic BP of < 90 mm Hg – signs of peripheral hypoperfusion – need for vasopressor or inotropic agents

Renal failure – serum creatinine level > 300 µmol/L– urine output < 500 mL/24 hr or < 180 mL/8 hr– need for hemo- or peritoneal dialysis.

Fagon JY et al .Intensive Care Med 1993; 19:137-144

Characterization of ICU patients using a model Characterization of ICU patients using a model based on the presence or absence of organ based on the presence or absence of organ dysfunctions and/or infectiondysfunctions and/or infection


Central nervous system failure – Glasgow Coma Scale score greater than 6 in the absence of

sedation – Sudden onset of confusion or psychosis.

Hepatic failure

– Serum bilirubin levels greater than 100 µmol/L– Alkaline phosphatase levels >3× the normal range.

Hematologic system failure

– Hematocrit level < 20%, – WBC < 2,000/mm3,– Platelet count of < 40,000/mm3.

Fagon JY et al .Intensive Care Med 1993; 19:137-144

Principles for managing patients Principles for managing patients

with acute pancreatitiswith acute pancreatitis

Assessing the severity remains the key Assessing the severity remains the key element in the initial assessment of element in the initial assessment of patients. patients.


with acute pancreatitiswith acute pancreatitis

Supportive care with close attention to volume status and electrolyte balance

Fasting of the patient

Pain management using narcotic agents. Predicting the severity of an attack and triaging of

patients to intensive care units or a regular floor

Bassi C, Cochrane Database of Systematic Reviews. 2003;(4):CD002941


with acute pancreatitis (Contwith acute pancreatitis (Cont‘d)‘d)

Early detection of complications

Prophylactic broad-spectrum antibiotics for patients with predicted severe pancreatitis

Identification of patients who may benefit from ERCP Identification of patients who may benefit from ERCP ( (when severe pancreatitis is complicated by progressive jaundice or when severe pancreatitis is complicated by progressive jaundice or cholangitischolangitis))

Adequate nutritional support

Bassi C, Cochrane Database of Systematic Reviews. 2003;(4):CD002941

Increased risk of post ERCP Increased risk of post ERCP PancreatitisPancreatitisPatient factors Sphincter of Oddi dysfunction Younger age Female sex History of prior post-ERCP pancreatitis

Procedure factors Low endoscopist experience Small common bile duct diameter Pancreatic sphincterotomy Difficult biliary cannulation Precut sphincterotomy Multiple cannulations Sphincter of Oddi manometry

Increased risk of post ERCP Increased risk of post ERCP PancreatitisPancreatitis

(1 – 10%)(1 – 10%)

1-2%1-2% after ERCP after ERCP 1-4%1-4% after biliary endoscopic after biliary endoscopic

sphincterotomy (ES)sphincterotomy (ES) 4-8%4-8% after pancreatic ES after pancreatic ES 13-35%13-35% after minor papilla ES after minor papilla ES

Prevention of post-ERCP Prevention of post-ERCP pancreatitispancreatitis

Not usefulNot useful Corticosteroids Antibiotics Anticholinergics Interleukin-10 Lexipafant Lidocaine sprayed on the ampulla of Vater Volume expansion with 10% Dextran-40


Potentially useful: Require further Potentially useful: Require further studiesstudies

SomatostatinSomatostatin Nitroglycerine Nitroglycerine DiclofenacDiclofenac intravenous secretinintravenous secretin High-dose allopurinolHigh-dose allopurinol Gabexate


Most usefulMost useful

Proper technique and patient selectionProper technique and patient selection

Pancreatic duct stenting in high risk patientsPancreatic duct stenting in high risk patients


SomatostatinSomatostatin

Inhibition of exocrine secretion of the pancreas, which plays an important role in the pathogenesis of acute pancreatitis.

Direct anti-inflammatory and cytoprotective

effects.

Uhl W, Buchler MW, Malfertheiner P et al. Gut. 1999;45:97-104.

Cavallini G et al, Dig Liver Dis. 2001;33:192-201.


Diclofenac

Diclofenac is a potent inhibitor of phospholipase A2, which regulates inflammatory mediators, including prostaglandins, leukotrienes, and platelet activating factor.

100 mg rectal diclofenac given immediately

after ERCP reduces the incidence of acute pancreatitis in patients at higher risk for post-ERCP pancreatitis

Murray B, et al. Gastroenterology 2003, 124:1786-1791.


NitroglycerineNitroglycerine

Transdermal glyceryl trinitrate patch placed

a half hour before the procedure and continued for 24 hours led to a reduction in post-ERCP pancreatitis

Moretó M, Zaballa M, Casado I, et al.: Gastrointest Endosc 2003, 57:1-7.

Pancreatic stenting in patients "at-Pancreatic stenting in patients "at-risk“ of post-ERCP pancreatitisrisk“ of post-ERCP pancreatitis

Problems

Inability to place a pancreatic duct stent

Ampullary trauma

Pancreatic duct changes

Need to repeat endoscopy to retrieve stents

Fazel A et al. Gastrointest Endosc 2003, 57:291-294.

Pancreatic stenting in patients "at-Pancreatic stenting in patients "at-risk“ of post-ERCP pancreatitisrisk“ of post-ERCP pancreatitis

Effective ??Effective ??

5 randomized controlled trials5 randomized controlled trials

Great reduction in the risk of post-ERCP pancreatitisGreat reduction in the risk of post-ERCP pancreatitis

Three-Fr gauge soft, unflanged, single pigtail pancreatic Three-Fr gauge soft, unflanged, single pigtail pancreatic stentsstents

Advantages and disadvantages of performing Advantages and disadvantages of performing ERCP to seal and stent a pancreatic duct ERCP to seal and stent a pancreatic duct disruption in patients with acute pancreatitis.disruption in patients with acute pancreatitis.

ProsPros

Pancreatic ductal disruption or Pancreatic ductal disruption or leak is a common event in leak is a common event in severe pancreatitis(37%)severe pancreatitis(37%)

Predicts a prolonged hospital Predicts a prolonged hospital stay.stay.

Treatment with a combination Treatment with a combination

ofof– Endoscopic stenting of the Endoscopic stenting of the

pancreatic ductpancreatic duct– Percutaneous drainsPercutaneous drains– Surgery as necessarySurgery as necessary

Safe, will promote healing of Safe, will promote healing of

the leak, and will improve the leak, and will improve patient outcome. patient outcome.

Advantages and disadvantages of performing Advantages and disadvantages of performing ERCP to seal and stent a pancreatic duct ERCP to seal and stent a pancreatic duct disruption in patients with acute pancreatitis.disruption in patients with acute pancreatitis.

ProsPros

Pancreatic ductal disruption or Pancreatic ductal disruption or leak is a common event in leak is a common event in severe pancreatitis(37%)severe pancreatitis(37%)

Predicts a prolonged hospital Predicts a prolonged hospital stay.stay.

Treatment with a combination Treatment with a combination

ofof– Endoscopic stenting of the Endoscopic stenting of the

pancreatic ductpancreatic duct– Percutaneous drainsPercutaneous drains– Surgery as necessarySurgery as necessary

Safe, will promote healing of Safe, will promote healing of

the leak, and will improve the leak, and will improve patient outcome. patient outcome.

AgainstAgainst

Lack of controlled dataLack of controlled data A subgroup of patients, A subgroup of patients,

– Pancreatic ascitesPancreatic ascites– Peripancreatic fluid Peripancreatic fluid

collectionscollections

May benefit from an ERCP May benefit from an ERCP usually after the first 2 weeksusually after the first 2 weeks

Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis

The mortality risk rises to >40% if sterile The mortality risk rises to >40% if sterile necrosis becomes superinfectednecrosis becomes superinfected

Window of opportunity of 1 – 2 weeksWindow of opportunity of 1 – 2 weeks

Strong evidence that intravenous antibiotic Strong evidence that intravenous antibiotic for 10 to 14 days decreased the risk of for 10 to 14 days decreased the risk of superinfection of necrotic tissue and superinfection of necrotic tissue and mortalitymortality

Indications for surgical interventionIndications for surgical intervention

No universally valid answerNo universally valid answer

Persistence of organ failure and/or systemic Persistence of organ failure and/or systemic inflammatory signs after 72 h of maximal inflammatory signs after 72 h of maximal supporting intensive care therapy is an supporting intensive care therapy is an indication for operative treatment. indication for operative treatment.

The timing of pancreatic The timing of pancreatic debridementdebridement

Controversial issueControversial issue Demarcation of pancreatic necrosis (2-3 w) is Demarcation of pancreatic necrosis (2-3 w) is

a precondition for sufficient debridementa precondition for sufficient debridement

Necrosectomy, performed later than three Necrosectomy, performed later than three weeks after the onset of disease higher weeks after the onset of disease higher rate of successful debridement of pancreatic rate of successful debridement of pancreatic necrosisnecrosis

Idiopathic Recurrent Acute Idiopathic Recurrent Acute PancreatitisPancreatitis

Laboratory analysis Laboratory analysis CFTR gene analysisCFTR gene analysis sweat chloride testsweat chloride test trypsin gene studiestrypsin gene studies duodenal aspiration for microcrystalsduodenal aspiration for microcrystals measurement of CA 19-9 and CEAmeasurement of CA 19-9 and CEA ERCP reveals a diagnosis in about 70% of patients with IRAP ERCP reveals a diagnosis in about 70% of patients with IRAP

after a negative initial evaluationafter a negative initial evaluation the procedure is not justified after the first episode of the procedure is not justified after the first episode of

pancreatitis,[pancreatitis,[ bile is aspirated for microcrystalsbile is aspirated for microcrystals SOM is performed when SOD is suspected, SOM is performed when SOD is suspected, minor papilla is cannulated when pancreas divisum is minor papilla is cannulated when pancreas divisum is

suspected.[75]suspected.[75]


EUS is increasingly used to evaluate patients with IRAP EUS is increasingly used to evaluate patients with IRAP EUS has equal or superior sensitivity to other commonly EUS has equal or superior sensitivity to other commonly

used tests in the diagnosis of microlithiasis and sludge.[used tests in the diagnosis of microlithiasis and sludge.[ SOD is detected using secretin-stimulated EUS by SOD is detected using secretin-stimulated EUS by

demonstrating persistent dilatation of the pancreatic demonstrating persistent dilatation of the pancreatic duct following secretin administrationduct following secretin administration

EUS has reasonable sensitivity and specificity in EUS has reasonable sensitivity and specificity in detecting structural lesions such as pancreas divisum] detecting structural lesions such as pancreas divisum] and an anomalous pancreatobiliary junction.[and an anomalous pancreatobiliary junction.[

Occult ampullary and pancreatic tumors may also be Occult ampullary and pancreatic tumors may also be discovered.[discovered.[

Finally, EUS can detect the presence of chronic Finally, EUS can detect the presence of chronic pancreatitis in patients initially presenting with IRAP.pancreatitis in patients initially presenting with IRAP.[57,58][57,58]


The primary value of MRCP for IRAP is in The primary value of MRCP for IRAP is in identifying anatomic abnormalities such as identifying anatomic abnormalities such as pancreas divisum, a choledochocele, pancreas divisum, a choledochocele, anomalous pancreatobiliary junction, or anomalous pancreatobiliary junction, or annular pancreasannular pancreas

MRCP may also detectMRCP may also detect neoplasianeoplasia chronic pancreatitischronic pancreatitis microlithiasismicrolithiasis its value for diagnosing these disorders has its value for diagnosing these disorders has

been minimally evaluated. been minimally evaluated.

Management of Idiopathic Management of Idiopathic Recurrent Acute PancreatitisRecurrent Acute Pancreatitis

Therapeutic options are limitedTherapeutic options are limited A number of "nonvalidated" therapies therefore exist for TIRAPA number of "nonvalidated" therapies therefore exist for TIRAP Smooth muscle relaxersSmooth muscle relaxers calcium-channel blockerscalcium-channel blockers nitrates, have been of limited utility in patients with SODnitrates, have been of limited utility in patients with SOD Pancreatic enzymes inhibitors Pancreatic enzymes inhibitors antioxidants, such asantioxidants, such as beta carotene,beta carotene, methionine,methionine, vitamin C, and vitamin E, may be beneficial by inhibiting the release of vitamin C, and vitamin E, may be beneficial by inhibiting the release of

oxygen-derived free radicals.[87]oxygen-derived free radicals.[87] pancreatic duct stents or endoscopic sphincterotomy (biliary or pancreatic) in pancreatic duct stents or endoscopic sphincterotomy (biliary or pancreatic) in

patients with TIRAP.[40,88] There is only 1 prospective, randomized trial to patients with TIRAP.[40,88] There is only 1 prospective, randomized trial to have evaluated the use of pancreatic duct stents for this indication.[89] have evaluated the use of pancreatic duct stents for this indication.[89] Patients randomized to stent placement suffered fewer episodes of Patients randomized to stent placement suffered fewer episodes of pancreatitis during the nearly 3-year follow-up. However, such therapy cannot pancreatitis during the nearly 3-year follow-up. However, such therapy cannot be widely supported outside of a research protocol until more data are be widely supported outside of a research protocol until more data are available.available.

empiric laparoscopic cholecystectomyempiric laparoscopic cholecystectomy Empiric administration of ursodeoxycholic acid and a low-fat dietEmpiric administration of ursodeoxycholic acid and a low-fat diet

Comparison between currently accepted Comparison between currently accepted and modified CT severity indexesand modified CT severity indexes

266 patients266 patients acute pancreatitis during a 1-year period acute pancreatitis during a 1-year period 66 66 underwent contrast-enhanced MDCT within 1 week of the onset of underwent contrast-enhanced MDCT within 1 week of the onset of

symptoms.symptoms.

Parameters Parameters

The length of the hospital stay (in days)The length of the hospital stay (in days)

The need for surgical interventionThe need for surgical intervention

The need for percutaneous intervention (aspiration and drainage)The need for percutaneous intervention (aspiration and drainage)

Evidence of infection in any organ system (positive results on a Evidence of infection in any organ system (positive results on a Gram stain or culture or the combination of a fever >100°F and an Gram stain or culture or the combination of a fever >100°F and an elevated WBC > 15,000/mm3)elevated WBC > 15,000/mm3)



The calcium-dependent intra-acinar cell activation of pancreatic The calcium-dependent intra-acinar cell activation of pancreatic digestive zymogens, particularly proteases, is an early event in the digestive zymogens, particularly proteases, is an early event in the initiation of acute pancreatitis. initiation of acute pancreatitis.

Activation of transcription factor NF-κB also occurs early in Activation of transcription factor NF-κB also occurs early in experimental pancreatitis..experimental pancreatitis..

expression of interleukin-6, tumor necrosis factor-α, and inducible expression of interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthasenitric oxide synthase

neurally mediated inflammation has an important role in acute neurally mediated inflammation has an important role in acute pancreatitis. Neurogenic inflammation is mediated by peripheral pancreatitis. Neurogenic inflammation is mediated by peripheral release of chemical transmitters, including substance Prelease of chemical transmitters, including substance P

inhibiting cyclo-oxygenase-2 by either pharmacologic inhibition or inhibiting cyclo-oxygenase-2 by either pharmacologic inhibition or gene deletion reduced pancreatitis severity and lung injurygene deletion reduced pancreatitis severity and lung injury

Leukotrienes play a role in inflammation, ischemia, and reperfusion. Leukotrienes play a role in inflammation, ischemia, and reperfusion. Use of a peptide leukotriene receptor antagonist to improve Use of a peptide leukotriene receptor antagonist to improve experimental acute pancreatitis has been described. Translation of experimental acute pancreatitis has been described. Translation of this research into prevention of ERCP-induced pancreatitis is noted this research into prevention of ERCP-induced pancreatitis is noted in this review. in this review.

ConclusionConclusion

increased understanding of early cellular events and the regulation increased understanding of early cellular events and the regulation of early and late inflammatory mediators. of early and late inflammatory mediators.

The importance of neuronal mediators has been demonstrated and The importance of neuronal mediators has been demonstrated and deserves further study. deserves further study.

Arachidonic acid metabolites are important mediators of local Arachidonic acid metabolites are important mediators of local inflammation and lung injury in experimental models. This has been inflammation and lung injury in experimental models. This has been translated into the use of diclofenac in prevention of post-ERCP translated into the use of diclofenac in prevention of post-ERCP pancreatitis. pancreatitis.

Local delivery of inflammatory inhibitors via the pancreatic duct Local delivery of inflammatory inhibitors via the pancreatic duct should be explored for the prevention of ERCP-induced pancreatitis, should be explored for the prevention of ERCP-induced pancreatitis, as should combination therapy that blocks Ca2+ mobilization, pH as should combination therapy that blocks Ca2+ mobilization, pH changes, and early transcription factors such as NF-κB. changes, and early transcription factors such as NF-κB.

Although progress continues in understanding of experimental Although progress continues in understanding of experimental pancreatitis and successfully attenuating the disease in the pancreatitis and successfully attenuating the disease in the laboratory, there has been difficulty in translating this research into laboratory, there has been difficulty in translating this research into therapy for clinical acute pancreatitis. therapy for clinical acute pancreatitis.

Better understanding of inflammatory cytokines, chemokines, and Better understanding of inflammatory cytokines, chemokines, and neurogenic mediators in experimental pancreatitis promises neurogenic mediators in experimental pancreatitis promises therapies to reduce pancreatic necrosis and lung injury in clinical therapies to reduce pancreatic necrosis and lung injury in clinical pancreatitis pancreatitis

Balthazar Computed Tomography Severity Balthazar Computed Tomography Severity

Index (CTSI)Index (CTSI)

Graded the severity of pancreatitis on the Graded the severity of pancreatitis on the basis of basis of – Degree of pancreatic inflammationDegree of pancreatic inflammation– Degree of pancreatic necrosis.Degree of pancreatic necrosis.

Correlated with Correlated with – MorbidityMorbidity– MortalityMortality

Not correlated with Not correlated with – organ failureorgan failure– peripancreatic complicationsperipancreatic complications

Balthazar EJ .et al Radiology 1990; 174:331—336. •

Jeddah Gut Club monthly meeting Yousef A. Qari Consultant Gastroenterologist King A.aziz University...

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